Formaldehyde → (3aR,6aR)-1-(4-Bromophenyl)-5-methyloctahydropyrrolo[3,4-b]pyrrole

To a solution of (3aR,6aR)-tert-butyl 1-(4-bromophenyl)hexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxylate (1.86 g, 5.1 mmol) in CH2Cl2 (50 mL) at 23° C. was added TFA (8 mL) and the mixture was allowed to stir for 2 hrs. The solvents were removed under vacuum and the residue was taken up in MeOH (50 mL) followed by the addition of formaldehyde (37%, 3 mL, 40 mmol) and NaBH3CN (950 mg, 15.1 mmol). The mixture was stirred at 23° C. for 10 hours, concentrated under reduced pressure and the residue was dissolved in CH2Cl2 (100 mL), washed sequentially with water (2×50 mL), brine (1×30 mL), and dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product mixture was purified via chromatography (SiO2, 0-10% MeOH in CH2Cl2) to provide the title compound. 1H NMR (300 MHz, CDCl3): δ=7.28 ppm (m, 2H), 6.44 (m, 2H), 4.05 (m, 1H), 3.45 (m, 1H), 3.19 (m, 1H), 2.94 (m, 1H), 2.67 (m, 1H), 2.52 (m, 3H), 2.30 (s, 3H), 2.16 (m, 1H), 1.95 (m, 1H). MS (ESI, M+1): 280.8.

1. customThe solvents were removed under vacuum
2. stirringThe mixture was stirred at 23° C. for 10 hours
3. concentrationconcentrated under reduced pressure
4. dissolutionthe residue was dissolved in CH2Cl2 (100 mL)
5. washwashed sequentially with water (2×50 mL), brine (1×30 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe crude product mixture was purified via chromatography (SiO2, 0-10% MeOH in CH2Cl2)

ORD record

ord-e11f26f37e7c42e890677b03345a9a9a

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399468B2